Novartis JAK Tus Taw Qhia Jakavi Ua tiav qhov kev kho Steroid-refractory Chronic Graft-tiv tiag-tus kab mob tiv thaiv kab mob (GvHD) Theem 3 Ntsuam Xyuas Zoo!

Novartis tsis ntev los no tau tshaj tawm cov ncauj lus ntxaws ntxaws ntawm qhov tseem ceeb Phase III REACH3 txoj kev kawm tseem ceeb (NCT03112603) ntawm 62 ntawm Lub Rooj Sib Tham 62 xyoos ntawm American Society of Hematology (ASH). Qhov no yog kev sib tw tsim, qhib-daim ntawv lo, ntau lub chaw tshawb nrhiav hauv cov menyuam yaus (≥12 xyoo) thiab cov neeg mob laus uas tau tsim cov tshuaj steroid-refractory lossis steroid-depend chronic graft-tiv tiag-tus kab mob (GvHD) tom qab hloov allogeneic qia cell hloov ntshav. Cov ntaub ntawv qhia tau hais tias piv nrog cov kev kho mob zoo tshaj plaws (BAT), qhov ncauj JAK1 / 2 inhibitor Jakavi (ruxolitinib) tau zoo dua ntawm cov kev ntsuas qhov ua tau zoo hauv cov neeg mob steroid refractory / dependant GvHD, suav nrog kev ua kom tsis muaj peev xwm tsis muaj txoj sia (FFS)) Thiab cov tsos mob qhia los ntawm tus neeg mob.

Chronic GvHD yog ib qho kev phom sij txog lub neej txoj sia ntawm kev hloov qia ua pob, thiab li ib nrab ntawm cov neeg mob yuav tshwm sim steroid refractory / dependence. Nws yog tsim nyog teev tias Jakavi yog thawj cov tshuaj los qhia qhov ua tau zoo hauv kev kho mob ntawm steroid-refractory / dependant GvHD hauv kev kho mob ntau qhov kev soj ntsuam. Raws li cov txiaj ntsig ntawm txoj kev tshawb nrhiav REACH3, Novartis npaj yuav xa daim ntawv thov kev tswj hwm rau Jakavi los kho cov tshuaj steroid-refractory / cov neeg mob GvHD nyob hauv cov teb chaws sab nraud Tebchaws Asmeskas hauv Tebchaws Europe thaum thawj ib nrab xyoo 2021.

Robert Zeiser, Lub Chaw Haujlwm Hematology, Oncology thiab Qia Hlawv Hloov Pauv, Tsev Kho Mob Tsev Kawm Ntawv ntawm Freiburg, Lub Tebchaws Yelemees, tau hais tias: "Kev puas tsuaj thiab muaj peev xwm ua rau muaj kev phom sij txog kev mob GvHD tom qab lub cev qia hloov tau coj txoj kev nyuaj loj rau kev kho mob, tshwj xeeb tshaj yog yuav luag ib nrab ntawm cov neeg mob. Rau cov neeg mob uas tsis tau teb txaus rau kev kho mob steroid. Raws li kev tshawb pom qhov tseeb REACH3 qhov txiaj ntsig, tam sim no peb muaj cov qauv tshiab ntawm kev saib xyuas rau cov neeg mob no."

Hauv txoj kev tshawb nrhiav REACH3, ntawm 24 lub lim tiam ntawm kev kho mob, qhov kev tshawb fawb tau mus txog qhov kawg: Thaum piv nrog pawg BAT, qhov feem ntau ntawm cov lus teb (ORR) ntawm pab pawg Jakavi tau zoo dua (49.7% vs 25.6%, p< 0.0001).="" ntxiv="" rau="" qhov="" no,="" jakavi="" tseem="" qhia="" txog="" kev="" muaj="" nuj="" nqi="" thiab="" kev="" kho="" mob="" tseem="" ceeb="" nyob="" rau="" hauv="" cov="" tseem="" ceeb="" kawg:="" (1)="" piv="" nrog="" pawg="" bat,="" pab="" pawg="" jakavi="" muaj="" qhov="" tsis="" ua="" kom="" tsis="" muaj="" txoj="" sia="" nyob="" (ffs;="" txhais="" tau="" tias="" muaj="" kev="" pib="" mob="" ntxov="" thiab="" pib="" kho="" cov="" kab="" mob="" tshiab.="" kev="" kho="" mob="" ntawm="" gvhd="" ntev,="" kev="" tuag="" ntawm="" kev="" tuag)="" pom="" tias="" muaj="" kev="" txhim="" kho="" tseem="" ceeb="" (nruab="" nrab="" ffs:="" qis="" dua="" 5.7="" hli;="" hr="0.370;" 95%="" ci:="" 0.268-0.510;="">< 0.0001).="" (2)="" raws="" li="" tau="" hloov="" kho="" lee="" cov="" tsos="" mob="" tau="" qhab="" nia="" (mlss)="" hloov="" pauv,="" qhov="" feem="" pua="" ​​ntawm="" cov="" neeg="" teb="" uas="" muaj="" cov="" qhab="" nia="" cim="" tag="" nrho="" (tss)="" raug="" txo="" los="" ntawm="" points7="" cov="" ntsiab="" lus="" los="" ntawm="" cov="" hauv="" paus="" tau="" siv="" los="" ntsuas.="" cov="" tsos="" mob="" qhia="" los="" ntawm="" cov="" neeg="" mob="" hauv="" pab="" pawg="" neeg="" jakavi="" tau="" zoo="" dua="" li="" cov="" uas="" nyob="" hauv="" pawg="" bat="" (24.2%="" vs="" 11.0%;="" p="0.0011)." (3)="" 76.4%="" ntawm="" cov="" neeg="" mob="" hauv="" pab="" pawg="" neeg="" jakavi="" tau="" ua="" tiav="" cov="" lus="" teb="" tau="" zoo="" tshaj="" plaws="" (bor),="" thiab="" 60.4%="" hauv="" pawg="" bat="" (lossis="2.17;" 95%="" ci:="" 1.34-3.52).="" lub="" sijhawm="" nruab="" nrab="" ntawm="" cov="" lus="" teb="" (dor)="" tsis="" tau="" mus="" txog="" hauv="" pab="" pawg="" jakavi,="" thiab="" 6.24="" lub="" hlis="" ntawm="" pawg="">

Hauv qhov kev tshawb fawb no, tsis muaj cov cim qhia txog kev nyab xeeb tshiab, thiab qhov xwm txheej tsis zoo (AEs) tshwm sim los ntawm kev kho mob yog xwm yeem nrog kev paub txog kev nyab xeeb ntawm Jakavi. Cov kev pom tshwm sim ntau tshaj plaws hauv Jakavi pawg thiab pawg pawg BAT yog ntshav tshuaj (29.1% vs 12.7%), thrombocytopenia (21.2% vs 14.6%), ntshav siab (15.8% vs 12.7%) thiab kub taub hau (15.8% vs 9.5%). Txawm hais tias 37.6% thiab 16.5% ntawm cov neeg mob yuav tsum tau txhaj koob tshuaj ntawm Jakavi thiab BAT, cov neeg mob tsis kho vim AEs muaj tsawg (16.4% thiab 7%, feem). Cov neeg tuag tau zoo sib xws ntawm cov pab pawg kho mob (19% vs 16% BAT). Tus naj npawb ntawm kev tuag tshwm sim los ntawm kev mob siab ntev GvHD hauv Jakavi pawg tau nce siab dua me ntsis.

Graft tiv thaiv tus kab mob hu ua tus kab mob (GvHD) yog ib qho mob uas yuav muaj kev phom sij txog kev phom sij tom qab lub cev hloov ntshav qog tag nrho. Nws yog ib cov tshuaj tiv thaiv ntawm cov hlwb pub tawm tsam cov neeg tau txais cov hlwb li niaj zaus vim hais tias cov neeg pub ntshav pub dawb suav cov neeg tau txais txiaj ntsig li lub hlwb txawv teb chaws. Ob qhov tseem ceeb ntawm GvHD yog mob GvHD (tshwm sim tsis dhau 100 hnub tom qab hloov chaw) thiab GvHD ntev (tshwm sim hauv 100 hnub tom qab hloov chaw). Tom qab allogeneic qia cell hloov chaw, kwv yees li 50% ntawm cov neeg mob yuav muaj mob GvHD mob siab lossis mob ntev, lossis ob qho tib si. Cov tsos mob ntawm tus mob GvHD tuaj yeem cuam tshuam rau ntawm daim tawv nqaij, lub plab zom mov, daim siab, qhov ncauj, lub ntsws, thiab pob qij txha. Rau cov neeg mob uas tsis teb rau kev kho steroid thaum pib los yog txiav txim siab refractory los kho steroid, kev kho mob ntxiv yog qhov xav tau ceev.

Cov txiaj ntsig ntawm txoj kev tshawb nrhiav REACH3 ua tiav cov txiaj ntsig yav dhau los qhia txog cov txiaj ntsig tseem ceeb III REACH2 kawm ntawm Jakavi hauv kev kho mob GvHD zoo. Qhov tom kawg yog thawj theem III kawm kom ua tiav qhov kawg ntawm qhov kawg nyob rau hauv kev kho mob hnyav GvHD. Cov ntaub ntawv qhia tau hais tias: thiab cov kev kho mob zoo tshaj plaws Tau Muab piv nrog (BAT), Jakafi ua tau zoo dua hauv kev ntsuas kev ua tau zoo hauv cov neeg mob steroid refractory mob GvHD.

Thaum lub Tsib Hlis 2019, Tsoom Fwv Teb Chaws Asmeskas FDA tau pom zoo ruxolitinib (kev ua lag luam los ntawm Incyte hauv Asmeskas raws li kev lag luam tawm lub npe Jakafi) raws li cov txiaj ntsig ntawm ib leeg-tes rau qib II REACH1 kev kawm siv rau cov menyuam yaus thiab cov neeg laus 12 xyoos thiab laus dua los kho steroid- refractory acute Graft tiv thaiv tus kab mob hauv tuam tsev (GvHD). Nws yog tsim nyog teev tias ruxolitinib yog thawj cov tshuaj pom zoo los ntawm FDA los kho kho steroid-refractory GvHD. Hauv txoj kev tshawb nrhiav REACH1, tag nrho cov lus teb (ORR) ntawm ruxolitinib nyob rau 28 hnub ntawm kev kho mob yog 57%, thiab tus nqi teb tag nrho (CR) yog 31%.

Lub Plaub Hlis xyoo no, cov txiaj ntsig ntawm txoj kev tshawb nrhiav REACH2 tau tshaj tawm nyob rau hauv New England Journal of Medicine (NEJM): piv nrog pawg kho mob BAT, tus lej teb tag nrho (ORR) ntawm pab pawg kho mob Jakavi hnub 28 tau zoo dua (62% vs 39%, p< 0.001),="" ua="" tiav="" qhov="" kawg="" ntawm="" kev="" kawm.="" hais="" txog="" cov="" ntsiab="" lus="" tseem="" ceeb="" kawg,="" piv="" nrog="" pawg="" kho="" mob="" bat,="" qhov="" sib="" piv="" ntawm="" cov="" neeg="" mob="" hauv="" pawg="" neeg="" kho="" mob="" jakavi="" uas="" khaws="" tau="" cov="" tshuaj="" orr="" tsis="" pub="" dhau="" 8="" lub="" lis="" piam="" tau="" nce="" siab="" dua="" (40%="" vs="" 22%,="">< 0.001).="" ib="" qho="" ntxiv,="" qhov="" tsis="" ua="" haujlwm-tsis="" muaj="" sia="" nyob="" (ffs)="" ntawm="" pawg="" kho="" mob="" jakavi="" tau="" ntev="" dua="" li="" cov="" pab="" pawg="" kho="" mob="" bat="" (5.0="" hli="" vs="" 1.0="" lub="" hlis;="" hr="0.46," 95%="" ci:="" 0.35,="" 0.60),="" thiab="" lwm="" yam="" kev="" ua="" tiav="" theem="" kawg="" pom="" pom="" tias="" muaj="" txiaj="" ntsig="" zoo,="" suav="" nrog="" kev="" tos="" ntev="" ntev="">

ruxolitinib yog thawj qhov ncauj Janus kinase 1 thiab Janus kinase 2 (JAK1 / JAK2) inhibitor. Cov tshuaj' s cov cim qhia tam sim no muaj xws li: cov leeg pob txha, polycythemia vera (PV), corticosteroid-refractory mob hnyav ua rau tus mob tiv thaiv kab mob (GvHD). Hauv Asmeskas kev ua lag luam, cov tshuaj muaj npe yog Jakafi thiab muag los ntawm Incyte; sab nraud Asmeskas, cov tshuaj muaj npe lag luam zoo li Jakavi thiab muag los ntawm Novartis.

Tam sim no, Incyte tseem tab tom txhim kho ruxolitinib lee, uas yog nyob rau theem III kev txhim kho hauv chaw kho mob: (1) rau kev kho mob ntawm cov neeg mob uas tsis tshua muaj me ntsis mus rau atopic dermatitis (TRuE-AD project), (2) rau kev kho mob ntawm cov hluas thiab Cov Neeg Laus Vitiligo ( TRuE-V Project). Incyte muaj cov cai thoob ntiaj teb los tsim thiab ua lag luam muag ruxolitinib lee. Cov ntaub ntawv tshawb fawb txog qib II yav dhau los qhia tau hais tias piv nrog cov tswj kev tsav tsheb (tshuaj dawb tsis muaj tshuaj tua kab) pawg, cov neeg mob hauv ruxolitinib lee kho pab pawg tau txhim kho lub ntsej muag tseem ceeb ntawm cov qhab nia ua tau zoo, thiab cov kab mob ua haujlwm ntawm daim tawv nqaij (rov ua dua tshiab) muaj kev txhim kho tseem ceeb. Cov. Nyob rau lub Ob Hlis ntawm lub xyoo no, theem III qhov project ntawm ruxolitinib lee rau kev kho mob ntawm atopic dermatitis tau ua tiav.